Lipids in artificially-formulated infant milks differ markedly from those in human milk. In contrast to human milk, they contain little cholesterol, up to 55% polyunsaturated fat, and no very long chain polyenoates. Both polyunsaturated fat and cholesterol have been shown to alter plasma lipoprotein metabolism, especially low density lipoproteins (LDL); but effects of these variables on high density lipoprotein (HDL) apoproteins and lipids are not clear. Furthermore, while infants fed cows' milk (less than 1% linoleate) compared to those fed human milk ( 7-10% linoleate) have qualitative differences in membrane 20-22C polyenoates, infants fed these diets have similar amounts of fatty acids in membrane phospholipids with more than 18C. In a preliminary study, we found significantly less phosphatidylethanolamine (PE) and phosphatidylcoline (PC) fatty acids of more than 18C, compared to infants fed human milk. The double bond index of erythrocyte phospholipids, generally thought to be related to membrane fluidity, was significantly lower in infants fed SMA than in those fed human milk and Enfamil. Fatty acids in erythrocyte membranes are thought to be indicative of membrane lipids in general. We will study the effects of changes in the ratio of polyunsaturated to saturated (P/S) fat on plasma lipids, and HDL apoproteins and lipids; and erythrocyte PE, PC and sphingomyelin fatty acid in 4 1/2-6 mo. -old infants receiving at least 90% of energy as human milk (P/S=0.2) compared to SMA (P/S=0.5) or Enfamil (P/S=2.65). Monthly dietary histories are being obtained, and nutritional counseling given to mothers of infants to discourage addition of non-milk sources of energy. Preliminary data suggest that HDL apoproteins A-I and A-II, quantitated by radialimmunodiffusion using rabbit antihuman serum, are decreased by elevated dietary P/S ratios. Phospholipids are purified by TLC prior to analysis of their fatty acid compositions by GLC. The major lipids in plasma and HDL will be measured by standard microprocedures. The same determinations will be made on blood samples drawn from these same infants at 18 mos. A dietary coding system will be used to determine the intake of polyunsaturated to saturated fat, and additional dietary variables from a combination of dietary recall and usual intake histories. The effects of variation in P/S ratio on HDL metabolism are possibly relevant to arteriosclerosis.